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Tuberculosis (TB) is an infectious airborne disease caused by Mycobacterium tuberculosis. Since the 1990 s, many countries have made significant progress in reducing the incidence of TB and associated mortality by improving health services and strengthening surveillance systems. Nevertheless, due to the emergence of multidrug-resistant TB (MDR-TB), alongside extensively drug-resistant TB (XDR-TB) and TB-HIV co-infection, TB remains one of the lead causes of death arising from infectious disease worldwide, especially in developing countries and disadvantaged populations. Marine natural products (MNPs) have received a large amount of attention in recent years as a source of pharmaceutical constituents and lead compounds, and are expected to offer significant resources and potential in the fields of drug development and biotechnology in the years to come. This review summarizes 169 marine natural products and their synthetic derivatives displaying anti-TB activity from 2013 to the present, including their structures, sources and functions. Partial synthetic information and structure-activity relationships (SARs) are also included.
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Antituberculosos , Produtos Biológicos , Descoberta de Drogas , Mycobacterium tuberculosis , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Produtos Biológicos/síntese química , Antituberculosos/farmacologia , Antituberculosos/química , Antituberculosos/síntese química , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Relação Estrutura-Atividade , Estrutura Molecular , Testes de Sensibilidade Microbiana , Animais , Organismos Aquáticos/química , Tuberculose/tratamento farmacológicoRESUMO
The fungus Xylaria sp. Z184, harvested from the leaves of Fallopia convolvulus (L.) Á. Löve, has been isolated for the first time. Chemical investigation on the methanol extract of the culture broth of the titles strain led to the discovery of three new pyranone derivatives, called fallopiaxylaresters A-C (1-3), and a new bisabolane-type sesquiterpenoid, named fallopiaxylarol A (4), along with the first complete set of spectroscopic data for the previously reported pestalotiopyrone M (5). Known pyranone derivatives (6-11), sesquiterpenoids (12-14), isocoumarin derivatives (15-17), and an aromatic allenic ether (18) were also co-isolated in this study. All new structures were elucidated by the interpretation of HRESIMS, 1D, 2D NMR spectroscopy, and quantum chemical computation approach. The in vitro antimicrobial, anti-inflammatory, and α-glucosidase-inhibitory activities of the selected compounds and the crude extract were evaluated. The extract was shown to inhibit nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells, with an inhibition rate of 77.28 ± 0.82% at a concentration of 50 µg/mL. The compounds 5, 7, and 8 displayed weak antibacterial activity against Staphylococcus areus subsp. aureus at a concentration of 100 µM.
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Sesquiterpenos , Xylariales , Camundongos , Animais , Células RAW 264.7 , Xylariales/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos/isolamento & purificação , Óxido Nítrico/biossíntese , Óxido Nítrico/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Estrutura Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Lipopolissacarídeos , Testes de Sensibilidade Microbiana , Macrófagos/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificaçãoRESUMO
Thrombosis can lead to a wide variety of life-threatening circumstances. As current thrombolytic drug screening models often poorly predict drug profiles, leading to failure of thrombolytic therapy or clinical translation, more representative clot substrates are necessary for drug evaluation. Utilizing a Chandler loop device to form clot analogs at high shear has gained popularity in stroke societies. However, shear-dependent clot microstructure has not been fully addressed and low shear conditions are often overlooked. We herein characterized the impact of wall shear rate (126 to 951 s-1) on clot properties in the Chandler loop. Different revolutions (20-60) per minute and tubing sizes (3.2 to 7.9 mm) were employed to create different sized clots to mimic various thrombosis applications. Increased shear resulted in decreased RBC counts (76.9 ± 4.3% to 17.6 ± 0.9%) and increased fibrin (10 to 60%) based on clot histology. Increased fibrin sheet morphology and platelet aggregates were observed at higher shear under scanning electron microscope. These results show the significant impact of shear and tubing size on resulting clot properties and demonstrate the capability of forming a variety of reproducible in-vivo-like clot analogs in the Chandler loop device controlling for simple parameters to tune clot characteristics.
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Acidente Vascular Cerebral , Trombose , Humanos , Plaquetas , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/terapia , Fibrinolíticos , FibrinaRESUMO
Personalized medicine has gained much attention in the past decades, and identifying the effects of factors is essential for personalized preventions and treatments. Hypertension is a major modifiable risk factor for cardiovascular disease and is influenced by complex factors. In order to decrease the incidence of hypertension effectively, the subjects should be divided into subgroups according to their characteristics. In this study, we proposed to use a heterogeneous logistic regression combined with a concave fusion penalty to analyze the population-based survey data, including common influencing factors of hypertension. The analytic steps include: (1) identifying the most important predictor; (2) estimating subgroup-based heterogeneous effects. In the present context of primary hypertension data, the modeling results showed that the calculated prediction accuracy under our method was greater than 99%, while zero under the classical logistic regression. The findings could provide a practical guide for further individualized measures implementation.
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Doenças Cardiovasculares , Hipertensão , Humanos , Modelos Logísticos , Fatores de RiscoRESUMO
PURPOSE: This study aimed to investigate the prevalence, risk, and prognostic factors for synchronous liver metastasis (LM) in colorectal cancer (CRC) and to construct nomogram for predicting occurrence and prognosis of synchronous LM. METHODS: A total of 203,998 CRC patients who were registered in the SEER database between 2010 and 2016 were included. Logistic regression was used to analyze risk factors and Kaplan-Meier was used to estimate the overall survival of CRC patients with LM. Potential prognostic factors were identified by multivariable Cox regression. For predicting the risk for development and prognosis in CRC patients with LM, we constructed nomogram and the predictive performance was estimated by the receiver operating characteristics cure, the concordance index, and calibration curve. RESULTS: In total, 15.3% of the CRC patients (N = 31,288) had synchronous LM. Male gender, black, uninsured status, left colon, T4/T1, and bone and lung metastases were positively associated with synchronous LM risk. The 1-year, 3-year, and 5-year overall survival rate was 49.1%, 18.4%, and 9.2%, respectively. Older age, male gender, black, uninsured status, poor histological differentiation, lymphatic metastasis, T4/T1, positive carcinoembryonic antigen, and lung, bone, and brain metastases were associated with the overall survival. Nomogram was constructed to predict the development and prognosis of synchronous LM and both of them were proved to have good calibration and discrimination. CONCLUSION: LM is highly prevalent in CRC patients. Nomogram basing on the risk and prognostic factors for synchronous LM was proved to have good performance for predicting the probability of LM occurrence and prognosis.
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Neoplasias Colorretais , Neoplasias Hepáticas , Idoso , Humanos , Metástase Linfática , Masculino , Nomogramas , PrognósticoRESUMO
Variants in the prostate stem cell antigen (PSCA) gene have been linked with risk of multiple cancers and other diseases. But results have been inconclusive and no systematic research synopsis has been available. We did a comprehensive meta-analysis to investigate associations between variants in this gene and risk of nine cancers and four nonneoplastic diseases based on data from 55 publications including 81 961 cases and 442 932 controls. We graded levels of cumulative epidemiological evidence of a significant association using the Venice criteria and false-positive report probability tests. We performed functional annotation for these variants using data from the Encyclopedia of DNA Elements Project and other public databases. We found that six variants were nominally significantly associated with an increased or reduced risk of three cancers and three nonneoplastic diseases (P < 0.05). Cumulative evidence of an association was graded as strong for rs2294008 [odds ratio (OR) = 1.32, P = 5.1 × 10-33], rs2976392 (OR = 1.29, P = 1.8 × 10-8), rs9297976 (OR = 0.75, P = 1.4 × 10-7), rs2976391 (OR = 1.38, P = 6.1 × 10-5) and rs138377917 (OR = 0.53, P = 0.008) with gastric cancer, rs2294008 with bladder cancer (OR = 1.15, P = 8.0 × 10-19), gastritis (OR = 1.35, P = 1.2 × 10-5), duodenal ulcer (OR = 0.68, P = 2.4 × 10-57) and gastric ulcer (OR = 0.88, P = 1.7 × 10-7). Data from the Encyclopedia of DNA Elements Project and other databases showed that these variants and other variants correlated with them might fall in putative functional regions. In conclusion, this study provides summary evidence that variants in the PSCA gene are associated with risk of gastric and bladder cancer, gastritis, as well as duodenal and gastric ulcer and highlights the significant role of this gene in the pathogenesis of these diseases.
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Antígenos de Neoplasias/genética , Proteínas de Neoplasias/genética , Neoplasias/etiologia , Úlcera Duodenal/etiologia , Proteínas Ligadas por GPI/genética , Predisposição Genética para Doença , Humanos , Neoplasias/genética , Risco , Neoplasias Gástricas/etiologia , Úlcera Gástrica/etiologia , Neoplasias da Bexiga Urinária/etiologiaRESUMO
Viscoelastic transformation of tissue drives aberrant cellular functions and is an early biomarker of disease pathogenesis. Tissues scale a range of viscoelastic moduli, from biofluids to bone. Moreover, viscoelastic behavior is governed by the frequency at which tissue is probed, yielding distinct viscous and elastic responses modulated over a wide frequency band. Existing tools do not quantify wideband viscoelastic spectra in tissues, leaving a vast knowledge gap. We present wideband laser speckle rheological microscopy (WB-SHEAR) that reveals elastic and viscous response over sub-megahertz frequencies previously not investigated in tissue. WB-SHEAR uses an optical, noncontact approach to quantify wideband viscoelastic spectra in specimens spanning a range of moduli from low-viscosity fibrin to highly elastic bone. Via laser scanning, micromechanical imaging is enabled to access wideband viscoelastic spectra in heterogeneous tumor specimens with high spatial resolution (25 micrometers). The ability to interrogate the viscoelastic landscape of diverse biospecimens could transform our understanding of mechanobiological processes in various diseases.
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Elasticidade , Reologia , Viscosidade , Reologia/métodos , Humanos , Animais , Lasers , Microscopia/métodosRESUMO
OBJECTIVE: It is crucial to conduct systematic reviews (SRs) and meta-analyses (MAs) to make causal references, in order to inform the clinical guidelines and decision-making. The high reporting quality of reviews through compliance with the guidelines Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Assessing the Methodological Quality of Systematic Reviews-2 (AMSTAR-2) could promote the consistency and reproducibility across the published articles. The purpose of this meta-epidemiological study is to evaluate the reporting methodological quality of SRs on the association between sleep duration and hypertension. METHODS: An electronic search in an online database was performed to retrieve systematic reviews and meta-analyses published up to 31st December 2022. Data screening and extraction were conducted by two investigators. The reporting quality of each included article was measured with reference to the 27-item 2020 PRISMA checklist, and methodological quality was evaluated using the AMSTAR-2. PRISMA evaluation was determined by total scores of individual SR and items scores and AMSTAR-2 assessment was also conducted using four categories. RESULTS: Of 2269 articles captured in the initial search, 15 SRs were included in the final analyses. All SRs had more than one incomplete PRISMA item. The mean of total scores was 20.5 (range 14-25), and the results of the AMSTAR-2 assessment were critically low to low. The reporting quality of "rationale," "objectives," "selection process," "study selection," "discussion," and 'support' was fully reported. SRs that reported registration information and protocol had a higher PRISMA score than articles that reported certain deficiencies. From the results of the AMSTAR-2 assessment, the methodological quality of these SRs and MAs was critically low to low. None of the included literature provided a list of excluded articles, and the report of the search strategy was incomplete; half of the SRs did not use appropriate tools to assess the risk of bias in each included study. CONCLUSIONS: Both the reporting and methodological quality of overall studies are less than ideal, with several key items being consistently under-reported. The quality measured by AMSTAR-2 is mainly consistent with the quality of reporting. Authors, reviewers, and journal editors should raise awareness and move forward to encourage completeness of SR reporting based on the results, which can aid in enhancing the quality of evidence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023459901.
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Hipertensão , Metanálise como Assunto , Duração do Sono , Revisões Sistemáticas como Assunto , Humanos , Projetos de PesquisaRESUMO
BACKGROUND: We aimed to prospectively examine the association of baseline allostatic load (AL) and longitudinal AL changes with incident cardiovascular disease (CVD) and all-cause mortality among middle-aged and elderly Chinese populations and evaluate the relative contributions of each physiological system of AL. METHODS: Data from the China Health and Retirement Longitudinal Study (CHARLS) among adults aged 45 years or older were analyzed. Cox regression models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) for the associations between baseline AL/longitudinal AL changes with incident CVD and all-cause mortality. RESULTS: Compared with adults with AL 0-1, HRs of those with baseline AL 2-3 and AL ≥ 4 were 1.24 (95 % CI: 1.06, 1.45) and 1.51 (95 % CI: 1.27, 1.80) for incident CVD, and 1.39 (95 % CI: 1.11, 1.75) and 2.02 (95 % CI: 1.60, 2.54) for all-cause mortality. Similar results were found when we treated baseline AL as a continuous variable. We also found per AL score increase during 4 years of follow-up was related to a 11 % (HR, 1.11; 95 % CI: 1.03, 1.20) and 21 % (HR, 1.21; 95 % CI: 1.10, 1.34) increase in incident CVD and all-cause mortality, respectively. LIMITATIONS: Self-reported physician-diagnosed CVD was used to assess the incident CVD. CONCLUSIONS: Both baseline AL and longitudinal increases in AL were positively associated with incident CVD and all-cause mortality in middle-aged and elderly adults. Individuals with high AL need to be dynamically monitored for CVD and pre-mature mortality prevention.
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Alostase , Doenças Cardiovasculares , Idoso , Adulto , Pessoa de Meia-Idade , Humanos , Doenças Cardiovasculares/epidemiologia , Estudos Longitudinais , Estudos de Coortes , Fatores de RiscoRESUMO
A great need exists for the development of a more representative in-vitro model to efficiently screen novel thrombolytic therapies. We herein report the design, validation, and characterization of a highly reproducible, physiological scale, flowing clot lysis platform with real-time fibrinolysis monitoring to screen thrombolytic drugs utilizing a fluorescein isothiocyanate (FITC)-labeled clot analog. Using this Real-Time Fluorometric Flowing Fibrinolysis assay (RT-FluFF assay), a tPa-dependent degree of thrombolysis was observed both via clot mass loss as well as fluorometrically monitored release of FITC-labeled fibrin degradation products. Percent clot mass loss ranged from 33.6% to 85.9% with fluorescence release rates of 0.53 to 1.17 RFU/min in 40 and 1000 ng/mL tPa conditions, respectively. The platform is easily adapted to produce pulsatile flows. Hemodynamics of human main pulmonary artery were mimicked through matching dimensionless flow parameters calculated using clinical data. Increasing pressure amplitude range (4-40 mmHg) results in a 20% increase of fibrinolysis at 1000 ng/mL tPA. Increasing shear flow rate (205-913 s-1) significantly increases fibrinolysis and mechanical digestion. These findings suggest pulsatile level affects thrombolytic drug activities and the proposed in-vitro clot model offers a versatile testing platform for thrombolytic drug screening.
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Mechanical transformation of tissue is not merely a symptom but a decisive driver in pathological processes. Comprising intricate network of cells, fibrillar proteins, and interstitial fluid, tissues exhibit distinct solid-(elastic) and liquid-like (viscous) behaviours that span a wide band of frequencies. Yet, characterization of wideband viscoelastic behaviour in whole tissue has not been investigated, leaving a vast knowledge gap in the higher frequency range that is linked to fundamental intracellular processes and microstructural dynamics. Here, we present wideband Speckle rHEologicAl spectRoScopy (SHEARS) to address this need. We demonstrate, for the first time, analysis of frequency-dependent elastic and viscous moduli up to the sub-MHz regime in biomimetic scaffolds and tissue specimens of blood clots, breast tumours, and bone. By capturing previously inaccessible viscoelastic behaviour across the wide frequency spectrum, our approach provides distinct and comprehensive mechanical signatures of tissues that may provide new mechanobiological insights and inform novel disease prognostication.
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Objectives: Previous studies reported that there were disparities in hypertension management among different ethnic groups, and this study aimed to systematically determine the prevalence, awareness, treatment, and control rates of hypertension in multiple Chinese ethnic groups. Methods: We searched Embase, PubMed, and Web of Science for articles up to 25 October, 2022. The pooled prevalence, awareness, treatment, and control rates of hypertension were estimated with 95% confidence intervals (CI). The heterogeneity of estimates among studies was assessed by the Cochran Q test and I 2 statistic. Meta-regression analyses were conducted to identify the factors influencing the heterogeneity of the pooled prevalence, awareness, treatment, and control rate of hypertension. Results: In total, 45 publications including 193,788 cases and 587,826 subjects were eligible for the analyses. The lowest prevalence was found in the Han group (27.0%), and the highest prevalence was in the Mongolian population (39.8%). The awareness rates ranged from 24.4% to 58.0% in the four ethnic groups. Both the highest treatment and control rates were found in the Mongolian population (50.6% and 16.0%, respectively), whereas the Yi group had the lowest control rate (8.0%). In addition, the study year, the mean age of subjects, mean body mass index of subjects, tobacco use (%), alcohol use (%), residence (urban%), and education (primary school%) had varied effects on heterogeneity. Conclusions: These findings highlight the disparities in prevalence, awareness, treatment, and control rates of hypertension in a different ethnic population of China, which could provide suggestions for making targeted prevention measures.
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Using injectable hydrogels loaded with mesenchymal stem cells (MSCs) to repair chondral defects is a new trend of cartilage tissue engineering in recent years. In this study, hyaluronic acid (HA) hydrogels containing the system of sustained-release Kartogenin (KGN) and modified by RGD and HAV peptides were used to facilitate repair of cartilage defect in the knee joint of rabbits. Different groups of implants were injected into osteochondral defects, and samples were taken 4 weeks after operation. Through the qualitative and quantitative analysis of Micro-CT, it can be seen that both FH (unloaded cell group) and R + FH groups (allogeneic cell group) can repair osteochondral defects well, and the amount of bone formation is high, which is close to the intact cartilage groups. Macroscopic observation and histological staining analysis showed that except for the intact cartilage group, FH group obtained the highest score. The morphology of the cartilage tissue in the FH groups was more regular and continuous than that in R + FH and H + FH (xenogeneic cell group) groups, approaching that of native cartilage. Immunohistochemical staining of Collagen II (Col II) showed that the expression and morphology of Col II in FH groups were similar to those in intact cartilage tissue. Interestingly, through in vivo experiments, this functionalized hyaluronic acid hydrogel can effectively promote the rapid repair of rabbit knee cartilage defects within one month.
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Cartilagem Articular , Animais , Coelhos , Cartilagem Articular/patologia , Hidrogéis , Ácido Hialurônico , Células-Tronco , Engenharia Tecidual , Articulação do Joelho/cirurgia , ColágenoRESUMO
The difference in age structure and aging population level was an important factor that caused the difference in COVID-19's case fatality rate (CFR) in various regions. To eliminate the age effect on estimating the CFR of COVID-19, our study applied nonlinear logistic model and maximum likelihood method to fit the age-fatality curves of COVID-19 in different countries and regions. We further computed the standardized mortality ratio from the age-fatality curves of COVID-19 in the above regions and found that the risk of COVID-19 death in Wuhan was of a moderate level, while the non-Hubei region was even lower, compared with other regions. Regarding the disparity of CFRs among different regions in the country, we believed that there might be an unascertained phenomenon in high-endemic regions. Based on age-fatality rate curves, we estimated unascertained rates in cities with severe epidemics such as Wuhan and New York, and it was found that the total unascertained rates in Wuhan and New York were 81.6% and 81.2%, respectively. Meanwhile, we also found that the unascertained rates varied greatly with age.
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Neurovascularized bone regeneration remains an enormous challenge in the clinic. Biomaterials mimicking the developmental microenvironment might be promising tools to enhance tissue regeneration. In this study, functionalized hydrogel-microsphere composites are developed to enhance bone regeneration via a recapitulating neurovascularized microenvironment. RGD peptide and the porous structure generated by the degradation of gelatin microspheres (GMs) are beneficial for the proliferation and migration of human mesenchymal stem cells (hMSCs); mesoporous silica nanoparticles (MSNs) promote osteogenic differentiation of hMSCs through the delivery of BFP-1 peptide; the QK peptide from the GMs is sustained-released to recruit endogenous endothelial cells (ECs), and IK19 peptide grafted on the hydrogel guides the neurite outgrowth. The in vivo results show that the hydrogel-microsphere composites not only promote new bone formation, but also facilitate nerve infiltration and angiogenesis. Furthermore, the neurovascularized niche created by this composite stimulated neurite growth through MAPK, PI3K, IL17 and TNF signaling pathways, enabling vascularized bone regeneration. The findings suggest a novel bioengineering approach to guide the construction of neurovascularized bone repair materials, which is beneficial for achieving functional bone regeneration and repair.
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Células-Tronco Mesenquimais , Osteogênese , Humanos , Osteogênese/fisiologia , Hidrogéis/química , Microesferas , Células Endoteliais , Regeneração Óssea , Peptídeos/química , Crescimento NeuronalRESUMO
There is an emerging interest in utilizing synthetic multivalent inhibitors that comprise of multiple inhibitor moieties linked on a common scaffold to achieve strong and selective enzyme inhibition. As multivalent inhibition is impacted by valency and linker length, in this study, we explore the effect of multivalent benzamidine inhibitors of varying valency and linker length on plasmin inhibition. Plasmin is an endogenous enzyme responsible for digesting fibrin present in blood clots. Monovalent plasmin(ogen) inhibitors are utilized clinically to treat hyperfibrinolysis-associated bleeding events. Benzamidine is a reversible inhibitor that binds to plasmin's active site. Herein, multivalent benzamidine inhibitors of varying valencies (mono-, bi- and tri-valent) and linker lengths (â¼1-12â nm) were synthesized to systematically study their effect on plasmin inhibition. Inhibition assays were performed using a plasmin substrate (S-2251) to determine inhibition constants (Ki). Pentamidine (shortest bivalent) and Tri-AMB (shortest trivalent) were the strongest inhibitors with Ki values of 2.1±0.8 and 3.9±1.7â µM, respectively. Overall, increasing valency and decreasing linker length, increases effective local concentration of the inhibitor and therefore, resulted in stronger inhibition of plasmin via statistical rebinding. This study aids in the design of multivalent inhibitors that can achieve desired enzyme inhibition by means of modulating valency and linker length.
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Benzamidinas , Fibrinolisina , Fibrinolisina/química , Fibrinolisina/metabolismo , Benzamidinas/farmacologiaRESUMO
Metabolic dysfunction of ß-cells has been implicated as a contributor to diabetes pathogenesis, and efforts are ongoing to optimize analytical techniques that evaluate islet metabolism. High-resolution respirometry offers sensitive measurements of the respiratory effects of metabolic substrates and customizable manipulation of electron transport chain components, though the delicate nature of islets can pose challenges to conventional analyses. An affordable and reliable option for respirometry is the Oroboros Oxygraph-2 K system, which utilizes a stir bar to circulate reagents around cells. While this technique may be suitable for individual cells or mitochondria, the continual force exerted by the stir bar can have damaging effects on islet integrity. Herein, we demonstrate the protective benefits of a novel 3D-printed islet stabilization device and highlight the destructive effects of conventional Oxygraph analysis on islet integrity. Islet containment did not inhibit cellular responses to metabolic modulatory drugs, as indicated by robust fluctuations in oxygen consumption rates. The average size of wild-type mouse islets was significantly reduced following a standard Mito Stress Test within Oxygraph chambers, with a clear disruption in islet morphology and viability. Alternatively, containment of the islets within the interior chamber of the islet stabilization device yielded preservation of both islet morphology and increased cell viability/survival after respirometry analysis. Collectively, our study introduces a new and easily accessible tool to improve conventional Oxygraph respirometry of pancreatic islets by preserving natural islet structure and function throughout metabolic analysis.
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Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Animais , Sobrevivência Celular , Ilhotas Pancreáticas/metabolismo , Camundongos , Mitocôndrias/metabolismo , Consumo de OxigênioRESUMO
Hypertension (HTN) is a growing contributor to the global disease burden, and it is prevalent among people living at high altitudes (H-ALTs). This study aimed to explore the relationship between altitude and the prevalence of HTN among inhabitants living at H-ALTs. We searched electronic databases, including PubMed, Embase, and Web of Science, up to April 30, 2022. The quality of included studies was assessed using the Joanna Briggs Institute (JBI) checklist for prevalence studies. A total of 1273 articles were screened, and 32 studies (86,487 participants) were eligible for further analyses. The pooled prevalence among highlanders was 28.7%. General additive model (GAM)-based meta-regression analysis was conducted to explore the association between altitude and the prevalence of HTN. A curve-shaped line was found between altitude and the prevalence of HTN (ß = 0.998, p = 0.039) after adjusting for factors including publication year, sample size, age, sex, ethnic group, body mass index (BMI), smoking and alcohol consumption. The turning point was observed at 3300 m. The predictive parameter indicated that the smoothness and goodness of model fit were good (GCV = 0.014, R2 = 0.60, respectively). The findings may provide clues for further mechanistic studies that can improve HTN prevention among highlanders.